Preparation of secondary aromatic amines



PREPARATION OF SECONDARY AROMATIC AMINES No Drawing. Application April 18, 1955,

. SerialNo. 502,254 I 4 Claims. (Cl. 260-577) (Granted under Title 35, U. S. Code (1952), see. 266) Theinvention described herein may be manufactured and used by or for the Government of the United States of America for governmental purposes without the payment of any royalties thereon or therefor.

This invention relates to a new method for the production of secondary alkyl aromatic amines through the direct alkylation of primary aromatic amines with primary aliphatic alcohols.

It has been known that Raney nickel contains adsorbed hydrogen and a number of investigations based on the use of Raney nickel in hydrogenolysis without the addition of hydrogen have been reported in the literature. Among these investigations is that of Shah and coworkers, Proc. Indian Acad. Sci., 28A, 1942 (1948), in which benzidine sulfone is desulfurized with Raney nickel in the presence of ethanol and in which it was observed that the amino groups are alkylated to form the secondary amine, N,N-diethylbenzidine. A large amount of Raney nickel was employed in the reaction mixture, the weight ratio of Raney nickel to benzidine sulfone being to 1. This large amount of the Raney nickel can be attributed to the fact that it was used as the sole source of hydrogen for the reduction, although the known poisoning eifect of sulfur on nickel also comes into consideraiton and may in part account for the use of the large amount.

It has now been found that secondary alkyl aromatic amines of high purity can be obtained by the direct alkylation of primary aromatic amines with primary aliphatic monohydric alcohols using very small, catalytic amounts of Raney nickel, and without the addition of hydrogen.

The purity of the secondary aromatic amines obtained by the method of the invention is such that little or no tertiaryamine is present, and, after filtration to remove the nickel, they can be used directly in instances where a technical product may be employed. Purification of the secondary amines can be had by simple distillation or by -c rystallization from a suitable solvent. The yields of the crude secondary amine products derived from the use of the straight chain members of the primary aliphatic monohydric alcohols will run between about, 70 to 90%,. whereas the yields from the branched chain members are lower and will run from about- 40 to 50%;

p The amount of Raney nickel used in the alkylation method of the invention, based on the weight of the primary amino group or groups in the aromatic amine, is from about 0.5 to 6 parts 'by weight per part of primary amino group in the aromatic amine. basis, the amount of Raney nickel used by Shah nd co-workers, above, forthe desulfurization of hen" inc sulfone is about 77 parts by weight per part of primary amine group in the benzidine compound. In the practice of the new method, a large excess of the; primary saturated aliphatic alcohol is used to provide the necessary diluent for the reaction, although part of the alcohol maywbereplaced, insofar as it acts as On the samea diluent, by benzene, toluene or other suitable liquid diluent. The term excess is used herein in the customary sense of the word to mean an amount which is more than that theoretically required to satisfy the reaction. The preparation of the secondary amines is carried out by heating the primary aromatic amine in the presence of the Raney nickel andthe alcohol at reflux temperature until the reaction is completed. The time required for completion of the reaction will vary depending upon the amount of the Raney nickel used, smaller amounts requiring longer periods of time. The amounts of Raney nickel indicated above for use in the reaction represent a practical range determined, on the one hand, by the time factor involved in bringing the reaction to completion and, on the other, by the amount of the product which becomes adsorbed on the nickel. While larger amounts of Raney nickel can be used to hasten the time of completion of the reaction, the gain is offset to some extent by an increase in the amount of product adsorbed on the nickel. An extraction process is required for recovery of the product adsorbed. In general, completion of the alkylation of the primary aromatic amine can be attained within periods of time ranging from about 6 to 30 hours with the use of amounts of Raney nickel which are in inverse proportion within the above indicated range of from about 1 to 6 parts by weight per part of primary amino group in the aromatic amine. A preferred range of amounts of the Raney nickel for use in the method is from about 0.8 to 4.3 parts by weight per part of primary amino group in the aromatic amine. Use of the Raney nickel in these preferred amounts will provide a process in which completion of the reaction is eifeeted within about 6 to 30 hours with a minimum of the product adsorbed on nickel and yields of the secondary amine, including that recovered from the nickel, of from about 40 to The method of the invention is applicable to the preparation of secondary amines from mono and polynuclear primary aromatic amines which do not contain groups which are reducible under the conditions of the reaction. Groups of this kind are unsaturated aliphatic hydrocarbon, carboxyl, nitro, cyano, and sulfone groups. The aromatic amine may be a monoor polyamine and contain nuclearly substituted groups which do not undergo reduction under the conditions of the reaction, such as alkyl, aryl, aralkyl, alkoxy, aryloxy, aralkyloxy, alkylamino, arylamino, aralkylamino and alkyl-arylamino groups and halogen atoms. Among the primary aromatic amines which can be alkylated in accordance with the method of the invention to produce secondary amines are, for example, aniline, 1- and 2-naphthylamine, 1- and 2-aminoanthracene, o-, m-, and p-toluidine, o-, mand p-xylidine, p-cyclohexylaniline, o-, mand p-aminodiphenyl, 4-phenyl-l-naphthylamine, 2-amino-4-methyldiphenyl, 2- and 4 aminodibenzyl, 2 aminodiphenylmethane, o-, mand p-anisidine, o-, m and p-phenetidine, o-, mand p-aminodiphenylether, o-, mand p-phenylenediamine, 1,2- and 1,7-naphthylenediamine, benzidine, 4 methyl 1,2 napthalenediamine, 2,2 dimethoxybenzidine, 2,2-diaminodiphenylether, ethyl-o-, mand pphenylenediamine, o-, mand p-aminodiethylaniline, o-, mand p-aminotriphenylamine, o-, mand p-aminodiphenylamine, N-methyl-N-phenyl-p-phenylenediamine, oaminodibenzylaniline, and o-, mand p-bromo-, o-, mand p-chloro, o-, mand p-iodoand o-, mand p-fluoroaniline, l-bromo-Z-naphthylamihe, 4-bromoand 4'- chloro-4-aminodiphenylamine, etc.

The primary aliphatic monohydric alcohols which can be used for alkylation of the primary aromatic amines in accordance with the invention have the general formula ROH wherein R is an alkyl group of at least 2 carbon ethanol, propanol, butanol, isobutanol, pentanol, isopentanol, heptanol, octanol, 2-ethylhexanol, dodecanol, hexadecanol, octadecanol, benzyl alcohol, mor p-ethylbenzyl alcohol, etc. I 1

The mechanism of the overalI reaction of the new alkylation method is believed to be dehydrogenation of the primary alcohol to form the corresponding aldehyde, which then reacts with the primary aromatic amine to form either an alkylidine amine (Schilf base) or an a-hydroxyamine. Under the conditions of the method, a large surface of nickel saturated with hydrogen and a polar solvent (the alcohol) being present, both the Schiif base and/or the a-hydroxyamine may be hydrogenated to the corresponding secondary amine in accordance with the following general equation:

Raney Ni (Hg) Ar 2 RCHZOH ROHO RCHNHAI RCH=NAr I OH l H2 (4) 2( 2O) RCHZNHAP Evidence for the existence of the dehydrogenation step (1) was obtained when ethanol was refluxed over Raney nickel and the aldehyde vapors werepassed directly into a solution of 2,4-dinitrophenylhydrazine. The characteristic 2,4-dinitrophenylhydrazone of acetaldehyde began to precipitate within ten' minutes after refluxing had started. A similar experiment performed with aniline present in the reaction mixture resulted in the formation of the 2,4-dinitrophenylhydrazone of acetaldehyde only after about thirty hours of refluxing. Under the conditions of the experiment this was approximately the amount of time required to obtain the maximum yield of N-ethylaniline and, therefore, was roughly equal to the time necessary for the aniline to be consumed by reaction with the aldehyde. This is an indication that the aldehyde formed is a reactant and not simply a by-product. The presence of aldehyde in both benzyl and isopentyl alcohol reaction mixtures after refluxing was demonstrated by means of fuchsin-aldehyde and 2,4-dinitrophenylhydrazine tests.

The existence of the Schiff base as a possible inter mediate was shown when aniline was replaced with N- benzylideneaniline and benzyl alcohol was used as the reactant and solvent. N-benzylaniline was obtained in 81% yield.

The non-reactivity of methanol as a primary alcohol for the alkylation method may be explained by the fact no formaldehyde or formaldehyde derivative was isolated when methanol was refluxed over Raney nickel. With ethanol and the secondary alcohol, isopropanol, on the other hand, dehydrogenation took place and acetaldehyde and acetone, respectively, were isolated. The failure of acetone to react further can "be attributed to the lower degree of reactivity of the ketone as compared to the aldehyde. V

The Raney nickel used for the alkylation in accordance with the method of the invention is prepared by the method of Mozingo, R. Mozingo, Organic Synthesis, 21 15 (1947), and stored under absolute ethanol.

The following specific examples of the preparation of secondary aromatic amines are illustrative of the application of the new alkylation method and present a general procedure for the carrying out of the method.

Example 1 Raney nickel (which had been washed three times with 20 ml, portions of propauol to remove most of the bined filtrate and washings.

ethanol) and 100 ml. of propanol was stirred under reflux for 16 hours, cooled, and filtered (fluted Whatman No. 40 filter paper), and the nickel residue washed several times with 95 ethanol. The filtrate and the washings were combined and the alcohols removed by distillation at atmospheric pressure. The residue containing the secondary amine was distilled through a 25 cm. Vigreux .column under reduced pressure. The yield of N-propylaniline was 82%.

The yield of the secondary amines usually can be increased by extraction of the nickel residue with the combined filtrate and washings. In another synthesis of N- propylaniline performed in the manner of the above example, the reaction mixture after termination of refluxing, was filtered through the thimble in a Soxhlet apparatus, transfer being facilitated by means of 95% ethanol, and the nickel residue extracted for six hours with the com- Distillation of the extract gave a yield of 88% of N-propylaniline.

In the manner of Example 1, alkylation of aniline was carried out with ethanol, butanol, pentanol, hexanol and benzyl alcohol and with the branched chain alcohols, isobutanol and isopentanol to obtain the corresponding secondary amines. N-ethylaniline was obtained in 83% yield, N-butylaniline in 82% yield, N-pentylaniline in 82% yield, N-hexylaniline in 72% yield, N-benzylaniline in yield, N-isobutylaniline in 41% yield and N-isopentylaniline in 49% yield.

Example 2 Alkylation of benzidine was carried out in the manner of Example 1 using an excess of ethanol and 22.5 gr. (.122 mole) of benzidine. The combined filtrate and washings of the nickel residue was evaporated on a hot plate to a volume of about 100 ml. and the product allowed to crystallize slowly. The yield of crude product was 77%. On recrystallization from ethanol, the yield of N,N-diethylbenzidine was 63%.

Example 3 Butylation of benzidine was carried out in accordance with the general procedure set out in the above examples, using an excess of butanol and 15 grams of benzidine. The crude product amounted to 14.8 grams. On recrystallization from 95 ethanol, the yield was 12.5 grams or 52% of N,N'-dibutylbenzidine.

- The method of the invention is general in its application. Following the above general procedure, various secondary aromatic amines can be prepared from the primary amines and primary aliphatic alcohols as defined herein.

Since the invention described herein can be variously practiced without departing from the spirit and scope thereof, it is intended that specific embodiments of the invention appearing in the above description shall be taken as illustrative and not limiting of the scope of the invention except as may be defined in the following claims.

We claim:

1. In the method of alkylating primary aromatic amines with primary aliphatic alcohols to form secondary amines, the improvement which comprises heating the aromatic amine to reflux at atmospheric pressure with an amount of Raney nickel which is from about 0.5 to 6 parts by weight per part of primary amino group in the aromatic amine and an excess of primary alcohol of the general formula ROH wherein R is a member of the group consisting of alkyl radicals having at least 2 carbon atoms and aralkyl radicals, said primary aromatic amine being free from groups which undergo reduction in the reaction.

2. A method of alkylating primary aromatic amines as defined in claim 1, wherein the amount of Raney nickel present is from about 0.8 to 4.3 parts by weight per part of primary amino group in the aromatic amine.

3. A method of alkylating aniline to form secondary amines which comprises heating the aniline to reflux at atmospheric pressure with from about 0.5 to 6 parts by weight of Raney nickel per part of primary amino group of the aniline in an excess of an alkanol having at least 2 carbon atoms.

4. A method of alkylating benzidine to form secondary amines which comprises heating the benzidine to reflux at atmospheric pressure with from about 0.5 to 6 parts by weight of Raney nickel per part of primary amino group of the benzidine in an excess of an alkanol having at least 2 carbon atoms.

References Cited in the file of this patent UNITED STATES PATENTS 2,580,284 Deahl et a1. Dec. 25, 1951 OTHER REFERENCES Guyot et al.: Compt. Rend. vol. 189, pgs. 927-929 (1929).

Guyot et a1.: Soc. Chim. de France, vol. 47, pgs. 203- 210 (1930). 

1. IN THE METHOD OF ALKYLATING PRIMARY AROMATIC AMINES WITH PRIMARY ALIPHATIC ALCOHOLS TO FORM SECONDARY AMINES, THE IMPROVEMENT WHICH COMPRISES HEATING THE AROMATIC AMINE TO REFLUX AT ATMOSPHERIC PRESSURE WITH AN AMOUNT OF RANEY NICKEL WHICH IS FROM ABOUT 0.5 TO 6 PARTS BY WEIGHT PER PART OF PRIMARY AMINO GROUP IN THE AROMATIC AMINE AND AN EXCESS OF PRIMARY ALCOHOL OF THE GENERAL FORMULA ROH WHEREIN R IS A MEMBER OF THE GROUP CONSISTING OF ALKYL RADICALS HAVING AT LEAST 2 CARBON ATOMS AND ARALKYL RADICALS, SAID PRIMARY AROMATIC AMINE BEING FREE FROM GROUPS WHICH UNDERGO REDUCTION IN THE REACTION. 